Pulmonary II - Chronic Bronchitis and Emphysema Flashcards
General features of chronic bronchitis - what does a typical patient present like?
patient with persistent cough + sputum production for at least 3 mo in at least 2 consecutive years
simple chronic bronchitis
productive cough but no evidence of airway obstruction
chronic asthmatic bronchitis
intermittent bronchospasm, wheezing - hyper-reactive airways
obstructive chronic bronchitis (heavy smokers)
physiologic obstruction +emphysema
Pathogenesis of chronic bronchitis
–what are the two important factors?
two factors:
1) chronic irritation by inhaled substances,
2) microbiologic infections
4-10X more common in smokers
hypersecretion of mucus with mucous plugging
- –secondary obstruction to air flow
- –secondary infection
Chronic damage to the epithelium that occurs with chronic bronchitis can lead to …
metaplasia
- –large airways – squamous metaplasia
- –small airways – goblet cell metaplasia
Increased mucus production seen with chronic bronchitis
- -associated with …
- -what accompanying alterations are there?
associated with hypertrophy of submucosal glands in
trachea and bronchi
accompanying alterations small airways (2-3 mm)
–marked increase in goblet cells of small airways; mucus plugging of the lumen
–inflammatory infiltration
–fibrosis of the bronchiolar wall
–mucosal secretion is under autonomic (vagal) control;
?hypersecretion caused by neurohormonal pathways (also bronchoconstriction)
Pathogenesis of chronic bronchitis
- -causes
- -can coexist with
- -what is the role of infection
smoking and irritants also cause bronchiolitis - early
and relatively mild airflow obstruction
when bronchitis is accompanied by moderate to severe airflow obstruction, coexistent emphysema is the dominant lesion
role of infection is secondary
–not responsible for initiation of chronic bronchitis
–significant in maintaining bronchitis; acute
exacerbations
–cigarette smoke interferes with ciliary action
–also inhibits bronchial and alveolar leukocytes
Gross features of chronic bronchitis
hyperemia, swelling, bogginess of mucous
membranes
excessive mucinous to mucopurulent secretions
heavy casts of secretions and pus
Morphology of chronic bronchitis involving the large airways
enlargement of mucus-secreting glands of the trachea and bronchi (Reid Index)
- –ratio of the thickness of mucosal glands to the thickness of wall between the epithelium and the cartilage; normally < 0.4
- –increased in proportion to severity and duration of the disease
squamous metaplasia and dysplasia of large airways
Morphology of chronic bronchitis involving the small airways
marked narrowing of bronchioles - goblet cell metaplasia,mucous plugging, inflammation, and fibrosis
most severe cases - bronchiolitis obliterans
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General feature of emphysema
- -what is it?
- -how does this happen?
- -associations?
- -clinical ventilatory defects??
abnormal permanent enlargement of the airspaces distal to the terminal bronchiole
- -enlargement due to destruction of walls without obvious fibrosis (overinflation)
- –particularly destroying elastin
- -involves expansion of terminal bronchiole and acini, including alveolar ducts
–cleat-cut association with heavy cigarette
smoking
–clinical ventilatory deficits early, but not symptomatic until late
What are the two main issues with emphysema?
- Decreased FEV1
—collapse/obstruction of terminal airways on
expiration decreased FEV1 “pink puffers”
—can open airways OK, so well oxygenated
—symptoms occur only after extensive destruction of lung
tissue
—barrel-chested with faint breath sounds - Destruction of terminal airways;formation of bullae
- –Thin-walled coalescing of airspaces; not fibrotic
What are the different types of emphysema?
- Centriacinar (centilobular) emphysema
- Panacinar (panlobular) emphysema
- Paraseptal (distal acinar) emphysema
Centriacinar (centilobular) emphysema
central or proximal parts of the acini formed by the respiratory bronchioles
–both emphysematous and normal airspaces exist more common and severe in upper lobes (apical
segments)
–inflammation in septa with deposit of black pigment
–associated with smoking and chronic bronchitis, coal
worker’s pneumoconiosis
Panacinar (panlobular) emphysema
acini are uniformly enlarged including respiratory bronchiole and terminal blind alveoli
–prefix pan- refers to entire acinus, not entire lung
–occurs more commonly in lower zone and anterior
margins of lung
–most severe at bases
–associated with alpha1-antitrypsin deficiency
Paraseptal (distal acinar) emphysema
proximal portion of acinus is normal; distal portion dominantly involved
- -more striking adjacent to the pleura, along tissue septa, and margins of lobules
- -adjacent to areas of fibrosis, scarring, or atelectasis
- -more severe in upper half of lungs
- -multiple, continuous, enlarged airspaces to > 2.0 cm
- -?associated with spontaneous pneumothorax in young
Main theory in the pathogenesis of emphysema
- -what mechanism if responsible?
- -what does this mean in terms of the wall destruction?
- -what is the result of destruction?
protease-antiprotease mechanism
–alveolar wall destruction results from imbalance of
proteases (elastase) and anti-proteases
–increased protease activity leads to break-down of elastic components in the alveoli and airways
–results in loss of elastic recoil
–decreased spontaneous release of air from alveoli on expiration
–terminal airways collapse under positive expiratory pressures due to decreased structural components
Alpha-1 anti-tryspsin deficiency and emphysema relation
- -what kind of activity?
- -why is alpha 1 AT important?
- -where does the principle elastase come from?
This is due to decreased anti-elastase activity
- -homozygous patients with alpha1-antitrypsin develop emphysema
- –alpha 1-AT major inhibitor of proteases including elastase
- -principle elastase from neutrophils
- –neutrophils normally sequestered in lung (more in lower zones)
- –leads to elastase-mediated destruction of elastin
–The most important therapeutic intervention is cessation of smoking
Smoking and emphysema relation
- -what kind of activity?
- -what does smoking do to balance of cells?
- -what is nicotine’s role?
Increased elastase activity
- -smokers have greater numbers of neutrophils and macrophages in alveoli secondary to release of IL-8 from activated macrophages
- -nicotine is chemotactic for neutrophils and cigarette smoke activates the alternative complement pathway
- -smoking stimulates elastase from neutrophils and macrophages (macrophage elastase is NOT inhibited by alpha 1-AT)
- -oxidants in cigarette smoke and oxygen free radicals inhibit alpha 1-AT activity
Macroscopic morphology of emphysema
–what is the difference between panacinar and centrilobular?
panacinar emphysema - voluminous lungs
centrilobular emphysema - not as voluminous; upper
2/3 affected
large apical blebs or bullae characteristic of irregular emphysema secondary to scarring
Microscopic morphology of emphysema
abnormal fenestrations and destruction of septal walls
fusion of alveoli to form blebs or bullae
respiratory bronchioles and vasculature deformed and compressed by distortion of airspaces
Clinical features of emphysema
clinical manifestations do not appear until at least 1/3 of functioning parenchyma is incapacitated
dyspnea progresses; may see cough or wheezing
weight loss may be severe
slowing of forced expiration!!!!!!
barrel-chested with prolonged expiratory effort
Senile emphysema
age-related alterations of the internal geometry of the lung (larger alveolar ducts and smaller alveoli)
Obstructive oveinflation
trapping of air
Bullous emphysema
(>1 cm in distended state)
often apical, associated with scarring
may give rise to pneumothorax
Interstitial emphysema
entrance of air into connective tissue stroma, mediastinum, or subcutaneous tissue
